tbuckley/cabot-search huggingface dataset:
Abstract 12325: Burden of Premature Ventricular Complex is Associated With New-Onset Atrial Fibrillation
Authors: Po-Tseng Lee, Chih-Hui Hsu, Sheng-Hsiang Lin, Ping-yen Liu
Journal: Circulation (2022)

Introduction: Large burden of premature ventricular complex (PVC)lead to more cardiovascular mortality. A recent nationwide population-based database demonstrated that presence of PVC is associated with increased risk of atrial fibrillation. The relationship between burden of PVC and new onset of atrial fibrillation (AF), however, has never been investigated. Hypothesis: The purpose of the study is to clarify whether burden of PVC is associated with more new-onset AF. Methods: We designed a single-center, retrospective, and large population-based cohort to clarify the role of PVC burden and new-onset atrial fibrillation in Taiwan. PVC patients without history of atrial fibrillation with were divided into low burden group (&lt;1000/day) and moderate to high burden group (≥1000/day) based on the report of 24-h Holter ECG. New-onset AF was defined as new or first detectable events presenting as either persistent or paroxysmal AF. Results: A total of 16030 AF-naïve patients who underwent 24-h Holter ECG were enrolled in this study with a mean follow-up time of 973 days. A propensity-score matched analysis demonstrated moderate to high burden PVC group had a higher risk to have new-onset AF in comparison with low burden (4.96% vs 2.79%, p&lt;0.001). Multivariate Cox regression analysis showed that moderate to high burden of PVC is an independent risk factor to develop new-onset AF. A Kaplan-Meier analysis also showed that patients with moderate to high burden of PVC is associated with more new-onset AF (log rank p&lt;0.001). Conclusions: Burden of PVC is associated with new-onset atrial fibrillation. Patients with moderate to high burden PVC are at a higher risk to have new-onset atrial fibrillation.
Abstract 12018: Coronary Microvascular Dilatory Dysfunction According to the Types of Coronary Functional Abnormalitiescoronarymicrovascular Dilatory Dysfunction According to the Types of Coronary Functional Abnormalities
Authors: Hiroki Teragawa, Chikage Oshita, Yuko Uchimura
Journal: Circulation (2022)

Introduction: Recently, there has been an increasing interest in coronary functional abnormalities (CFA), which include epicardial coronary spasm (ECS), microvascular spasm (MVS) and microvascular vasodilatory dysfunction (MVD). However, the frequency of MVD according to the types of CFA remains unclear. Hypothesis: Thus, this study aimed to investigate the frequency of MVD according to the types of CFA in patients with ischemia with non-obstructive coronary arteries (INOCA). Methods: This study included 63 patients with INOCA who underwent coronary angiography (CAG) and coronary function tests (CFT) to evaluate chest pain. In CFT, acetylcholine was first administered intracoronarily in a stepwise manner, followed by chest symptoms, electrocardiographic ST-T changes and CAG. ECS was defined as coronary vasoconstriction of &gt;90% on CAG accompanied by chest symptoms or electrocardiographic ST-T changes. Additionally, a focal spasm was defined as a transient vessel narrowing of &gt;90% within the borders of one isolated coronary segment (as defined by the American Heart Association), and a diffuse spasm was defined as a 90% diffuse vasoconstriction in ≥2 adjacent coronary segments of the coronary artery. Moreover, MVS was defined as the presence of both chest symptoms and ST-T changes with non-significant coronary vasoconstriction (&lt;90%) on CAG. After nitroglycerin administration, coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) were subsequently obtained by transvenous adenosine triphosphate infusion using a pressure wire. MVD was defined as CFR of &lt;2.0 or IMR of ≥25 units. Results: CAG and CFT were performed on 91 coronary arteries in 63 patients with INOCA, the results of which are shown below. Conclusions: These findings suggest that the frequency of MVD differs according to the types of CFA. Properly evaluating the MVD and reflecting this in the therapeutic strategy in patients with INOCA is desirable in clinical settings.
Abstract 11592: Real-World Performance of Heartlogic Index in Subjects With CRT and ICD Devices
Authors: Ramesh Wariar, John Boehmer, Viktoria A Averina, Pramodsingh Thakur, Brian Kwan, Stephen B Ruble, Jagmeet Singh
Journal: Circulation (2022)

Introduction: The HeartLogic heart failure (HF) diagnostic was developed from data in subjects implanted with CRT-D devices. Diagnostic performance in subjects with ICDs (without CRT) is less well characterized. Objective: Compare HeartLogic performance in ICD and CRT subgroups. Methods: Data from US post-market HeartLogic CRT/ICD devices were directly linked with Medicare claims and subjects with continuous Medicare Part A&amp;B fee-for-service coverage were analyzed. Claims HF events (HFE) were defined using primary HF diagnosis codes (DRG 291-3, I50.xx) and included acute inpatient events, and outpatient events with IV diuretic therapy. Baseline characteristics included patient demographics, implant data, and claims chronic conditions flags (CCFs). Diagnostic performance was defined as the sensitivity to detect HFEs and the false-positive alert rate (FPR), from which a modified receiver operator characteristic (ROC) curve was generated. Continuous variables were expressed as mean±SD and categorical variables as proportions. Two-sided 95% confidence intervals (CI) were calculated for sensitivity (binomial distribution) and FPR (negative binomial model). Results: Out of 4190 subjects,1567 linked subjects were included in the analysis with an average follow-up of 1.4±0.5 years. The CRT group (N=1078, 69%) was more likely to be Caucasian (88% vs 82%), less likely to have de novo devices (62% vs 80%), more likely to have CCFs of AF (43% vs 33%) and congestive HF (89% vs 75%), and a HF hospitalization in the year prior to implant (23% vs 16%). CRT and ICD groups provided 296 and 139 HFEs for performance evaluation. HeartLogic ROCs were similar in both groups with no difference in the nominal sensitivity (83% [CI: 78, 87] vs 80% [72, 86%], p =0.41) or FPR (1.386 [CI: 1.337,1.511] vs 1.322 [1.238,1.488], p =0.41). Conclusions: HeartLogic diagnostic performance determined using real-world claims data was not different in subjects implanted with ICDs and CRT-Ds.
Abstract 11651: Machine Learning of Action Potential Shape to Define Refractory Periods in Ischemiccardiomyopathy
Authors: Samuel Ruiperez-Campillo, Brototo Deb, Anojan Selvalingam, Ruibin Feng, Prasanth Ganesan, Fleur V Tjong, Hui Ju Chang, Christopher Kowalewski, Maarten Z. H. Kolk, Paul L Clopton, Sunil K Vasireddi, Albert J Rogers, Sanjiv M Narayan
Journal: Circulation (2022)

Introduction: The effective refractory period (ERP) can characterize arrhythmic risk. To measure it clinically, a pacing protocol with 8-10 beats is required, preventing beat to beat analysis. Monophasic action potentials (MAP) can indicate ERP on every single beat (Fig A), but are often difficult to annotate due to a wandering baseline (Fig B). Hypothesis: We hypothesized that machine learning of ventricular MAPs could help identify instantaneous repolarization, without requiring manual measurement and without measuring time to drop to a specific repolarization voltage. Methods: We analyzed 5706 MAPs from 42 patients (age 65±13 Y) with ischemic cardiomyopathy in pacing. A multilayer perceptron (MLP) was developed to input MAP shapes and output action potential duration at 30, 60, 90% (MAPD 30,60,90) repolarization, indicating ERP. We used 60% of data in training, 20% in validation, 20% in testing. Results were compared to manual measurement. To identify which MAP regions were key to machine learning, we systematically perturbed MAP regions with white noise and assessed the drop in performance. Results: Errors between APD 30,60 and 90 from MLP and manual marking were 9.3(2.0), 5.8 (1.1) and 5.8 (0.7) ms respectively (fig. C). Fig D shows that MAP phases 0 and 3 were used by MLP to predict APD, as seen in the significant increase in error with perturbations in those MAP regions ( P &lt;0.05). Conclusions: Machine learning can directly indicate effective refractory periods by learning the electrogram shape of single beats, without extrastimuli or manual measurement. Explainability studies confirm that machines learn physiological data. This approach can be used to assess beat-to-beat characterization of atrial fibrillation patients.
Abstract 11497: Mineralocorticoid Receptor Antagonists and Atrial Fibrillation: A Systematic Review and Meta-Analysis
Authors: Alireza Oraii, Krzysztof Kowalik, Avinash K Pandey, Alexander P Benz, Jorge A Wong, David Conen, Jeff S Healey, William F McIntyre
Journal: Circulation (2022)

Introduction: Medical therapies to prevent atrial fibrillation (AF) episodes and to reduce heart failure (HF) or cardiovascular (CV) death in patients with AF are limited. The role of mineralocorticoid receptor antagonists (MRAs) in this population is unclear. Objectives: We aimed to assess whether the effect of MRAs (e.g. spironolactone, eplerenone, finerenone) in reducing cardiovascular events differs in patients with and without AF, and to evaluate the efficacy of MRAs in reducing AF events. Methods: We searched MEDLINE, Embase, and CENTRAL to March 2022 for randomized controlled trials (RCT) comparing an MRA to placebo or usual care in patients with established cardiovascular disease or risk factors. Pairs of reviewers systematically screened the eligible studies and used random-effects models to combine data. Results: We identified 6 RCTs including 7,245 participants (1,791 with AF and 5,454 without AF) that assessed the effect of MRAs on a composite of HF hospitalization or CV death (Figure). MRAs had similar efficacy for reducing HF hospitalization/CV death in patients with a history of AF (HR 0.86, 95% CI: 0.52-1.42; I 2 =71%) as compared to those without a history of AF (HR 0.77, 95% CI: 0.62-0.96; I 2 =58%) - P for subgroup differences=0.69. There was no evidence of difference in the efficacy of MRAs in reducing HF hospitalization (P for subgroup differences=0.93) and CV death (P for subgroup differences=0.41) in patients with and without AF. We identified 21 RCTs including 22,126 participants that reported on the occurrence of AF events. MRAs significantly reduced AF events (RR 0.78, 95% CI: 0.71-0.87; I 2 =0%). This effect was similar for reducing both new-onset AF (RR 0.81, 95% CI: 0.64-1.01; I 2 =32%) and recurrent AF episodes (RR 0.77, 95% CI: 0.67-0.88; I 2 =0%) - P for subgroup differences=0.71. Conclusions: MRAs reduce HF hospitalization or CV death to a similar extent in patients with and without AF. In addition, MRAs may prevent new-onset and recurrent AF events.
Abstract 12541: Development of a Transgenic Rabbit Model of Dravet Syndrome
Authors: Roberto Ramos-Mondragon, Chunling Chen, Julie Ziobro, Yan Chen, Shuyun Wang, Eric N Jimenez-Vazquez, Luis Lopez-Santiago, Jack Parent, Lori L Isom
Journal: Circulation (2022)

Introduction: Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of death in patients with epilepsy. While SUDEP mechanisms are not understood, there is evidence to implicate autonomic dysfunction and cardiac arrhythmias. Loss-of-function variants in SCN1A are linked to Dravet syndrome (DS). Importantly, SCN1A is expressed in both heart and brain in humans and rodents. Studies on Scn1a+/- DS mice and induced pluripotent stem cell (iPSC)-derived cardiac myocytes from DS patients show altered cardiac electrophysiology that serves as substrates for arrhythmias. However, no mouse or iPSC model can completely replicate the human DS phenotype. Hypothesis: Cardiac arrhythmias contribute to the mechanisms of SUDEP in a rabbit model of DS. Methods: We generate a New Zealand White (NZW) rabbit Scn1a deletion model using CRISPR-Cas9 gene editing. Rabbits were tested using video EEG/ECG telemetry as well as surface ECG under anesthesia. Optical mapping studies were performed in isolated hearts and patch clamp electrophysiology was performed in acutely isolated cardiac myocytes. Results: NZW Scn1a-/- kits died by postnatal day (P) 7-9 and showed bradycardia, long QT intervals, and AP prolongation. Cardiac myocytes isolated from NZW Scn1a+/- kits showed increased late sodium current compared to WT. We did not observe behavioral seizures or arrhythmias in NZW Scn1a+/- rabbits, which live normal life spans and breed normally. These data suggested, like mouse models, that the DS rabbit phenotype may be background strain dependent. To test this hypothesis, we crossed Scn1a+/- NZW rabbits to the Dutch Belted (DB) strain. We found that F1:NZW x DB Scn1a+/- rabbits have spontaneous seizures as well as pre- and post-ictal cardiac arrhythmia as assessed by video/EEG/ECG telemetry. Approximately 22% of the kits undergo premature death. Severe seizures are observed in adult animals, but to date no adults have died during seizures. Conclusions: F1:NZW x DB Scn1a+/- rabbits model DS in terms of seizures and SUDEP and are an optimal model to investigate neuro-cardiac mechanisms of SUDEP as well as to develop novel therapeutics for DS. To our knowledge, this is the first transgenic large animal model of a developmental and epileptic encephalopathy
Abstract 12222: The Significance of Concealed Fasciculo-Ventricular Connections in His Bundle Pacing
Authors: Rehan Mahmud, Eduardo Sternick, Damian Sanchez Quintana, Yolanda Macias, Shakeel Jamal, Beth Bailey, Marcos C De Almeida, Robert H Anderson
Journal: Circulation (2022)

Introduction: It is almost 100 years ago since Mahaim described so-called paraspecific connections between the ventricular conduction axis and the crest of the muscular ventricular septum, believing such pathways to be ubiquitous. Hypothesis: These pathways have yet to be considered as potential pathways for septal activation during His bundle pacing Methods: So as to explore the hypothesis that specialized septal pathways provide the substrate for septal activation during His bundle pacing, we compared the findings from 22 serially sectioned histological datasets and 96 different individuals undergoing pacing of the His bundle. Results: We found extensive histologically specialized pathways connecting the branching bundle with the crest of the muscular ventricular septum in almost four-fifths of the histological datasets. A delta wave was observed in nine-tenths of the individuals undergoing His bundle pacing. Capture of the delta wave varied according to voltage, a finding which correlated with the distance of the septal pathways from the site of penetration of the ventricular conduction axis. Ventricular activation times remained normal in the presence of the delta wave. A significant decrease in ventricular activation times was observed in individuals with disease of the ventricular conduction system. Conclusions: Analysis of the effect of delta wave on ventricular activation times permits us to conclude that His bundle pacing captures the fasciculo-ventricular connections initially described by Mahaim as being paraspecific and ubiquitous.
Abstract 12208: Acute Nitroglycerin Use Worsens Ventilatory Efficiency in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Bryce N Balmain, Andrew R Tomlinson, James P MacNamara, Satyam Sarma, Denis J Wakeham, Margot Morris, Raksa B Moran, Marcus Payne, Mitchel Samels, Benjamin D Levine, Tony G Babb
Journal: Circulation (2022)

Introduction: The marked rise in left ventricular (LV) filling pressure (ie., pulmonary capillary wedge pressure [PCWP]) during exercise and its association with adverse prognosis in patients with heart failure with preserved ejection fraction (HFpEF) has stimulated interest in therapies to decrease LV filling pressures. Although reducing LV filling pressure may improve exercise hemodynamics, this may also reduce pulmonary perfusion (Qc) and increase ventilation-perfusion (V/Q) mismatch, manifesting as an increase in ventilatory inefficiency during exercise (ie., slope of the ventilation [V̇ E ] and carbon dioxide elimination [V̇CO 2 ] relationship), which is a strong prognostic indicator of adverse outcomes in heart failure. Hypothesis: Reducing PCWP via acute nitroglycerin (NTG) treatment would increase the V̇ E /V̇CO 2 slope when compared with a placebo treatment in patients with HFpEF. Methods: 26 subjects were evaluated (age: 69±5y; BMI: 39.5±7.1kg/m 2 ; V̇O 2peak : 1.39±0.46L/min; 16 women/10 men). All subjects performed a six-minute constant-load cycling test at 20W with placebo or NTG treatment. PCWP was measured via a right-heart catheter, arterial blood gases were measured via a radial artery catheter, Qc was measured via direct Fick, and pulmonary gas exchange was measured via a customized breath-by-breath metabolic system. The V̇ E /V̇CO 2 slope was calculated as the relation between the rest-to-20W change in V̇ E and the rest-to-20W change in V̇CO 2 . Results: PCWP decreased with NTG at 20W (placebo: 20.8±5.8 vs. NTG: 16.4±5.1 mmHg, p=0.001). Qc also decreased with NTG at 20W (placebo: 8.69±1.84 vs. NTG: 8.26±1.87 L/min, p=0.01). In contrast, the V̇ E /V̇CO 2 slope increased with NTG (placebo: 37.5±5.8 vs. NTG: 39.6±7.0, p=0.01). Conclusions: These findings suggest that reducing LV filling pressure increases ventilatory inefficiency, possibly due to an increase in V/Q mismatch caused by a reduction in pulmonary perfusion. Since therapies to decrease LV filling pressure have gained considerable interest to improve exercise hemodynamics in HFpEF, further investigation is required to determine the clinical consequences of ventilation-perfusion mismatch and ventilatory inefficiency caused by a reduction in PCWP in these patients.
Abstract 11515: Mannose-Binding Lectin is Dysregulated in Cardiac Endothelial Cells of Women With Peripartum Cardiomyopathy
Authors: Zahra Aryan, Siavash Moghadami, Wei Wang, Junichi Sadoshima
Journal: Circulation (2022)

Introduction: Peripartum cardiomyopathy (PPCM) is a type of heart failure that presents with systolic dysfunction in the third trimester of pregnancy or early postpartum. Viral myocarditis, genetic predisposition, and hormonal changes are suggested as contributing factors to PPCM. However, the molecular basis of PPCM remained elusive. Hypothesis: Cardiac expression of genes involved in immune system response is dysregulated in PPCM. Methods: We identified women with PPCM and age/race-matched heart donors from a dataset obtained from Myocardial Applied Genomics Network (MAGNet) consortium. Left ventricular (LV) biopsies were taken at the time of heart transplantation. Bulk RNA-seq was performed on LV tissue of patients with PPCM and non-failing heart donors (NF). We used the Human Cell Atlas (HCA) reference database with accession code ERP128138 to investigate cell-specific enrichment of genes. Results: Mean age of study participants was 36.1 years and 33.3% of participants had African American ancestry. We found that LCN6 (Log2(fold_change) = -4.1, p-val = 0.0027) and FCN3 (Log2(fold_change) = -3.4, p-val = 0.0042) are downregulated in LV tissue obtained from PPCM compared to NF. LCN6 encodes lipocalin-6 and FCN3 encodes ficolin-3 which are upstream of the mannose-binding lectin complement pathway. Based on HCA dataset on adult human hearts, we observed that LCN6 and FCN3 genes are mainly expressed by endothelial cells. Conclusions: We demonstrated that expression of LCN6 and FCN3 genes, which are upstream of the mannose-binding lectin pathway, is decreased in cardiac endothelial cells of individuals with PPCM. Mannose-binding lectin is a soluble pattern recognition receptor that identifies mannose and N-acetylglucosamine residues in a wide variety of pathogens and antigen-antibody complexes and works as an opsonin that facilitates phagocytosis. Our findings suggest the possibility of impaired immune complex clearance in PPCM pathogenesis.
Abstract 12701: Structural Abnormalities and Arrhythmias - A Genetic Perspective
Authors: LakshmiPriya Uppalapati, Lisa D Wilsbacher, beth A whippo, Patricia Vassallo
Journal: Circulation (2022)

Introduction: Bicuspid aortic valves (BAV) are the most common congenital cardiac defect, with a prevalence of 1-2%. Further, 75% of BAV patients develop thoracic aortic aneurysm, which carries a nine-fold greater risk of dissection than the general population. Some BAV cases include a heritable component illustrated by a family history of BAV, but the underlying genes remain incompletely described. Our institution routinely refers patients with BAV and ascending aortic aneurysm/dissection for genetic testing. Clinical Case: A 43-year-old man presented to the Emergency Department with altered mental status; workup revealed a BAV and Stanford Type A Aortic Dissection (TAAD) that was emergently repaired. He was referred for genetic testing for TAAD and BAV as an outpatient. Eleven weeks post-operatively, he experienced multiple episodes of asymptomatic non-sustained ventricular tachycardia (NSVT) during cardiac rehabilitation. Given new NSVT, a cardiomyopathy and arrhythmia panel were added to his TAAD genetic testing panel. Results showed a pathogenic variant in PKP2 (c.2146-1G&gt;C); PKP2 is associated with autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC). Genetic testing also revealed a risk allele for drug-induced long QT (KCNE1 c.253G&gt;A [p.Asp85Asn]). No Pathogenic Variants or Variants of Uncertain Significance for BAV or TAAD were identified. Cardiac MRI showed no features of ARVC, and VT was not inducible during an electrophysiology study. Given lack of evidence of ARVC or inducible VT, an implantable loop recorder was placed rather than an ICD. The patient was counseled to inform providers of QT prolongation risk and recommend first-degree relative testing for pathologic mutations. Conclusion: Genetic testing panels should be selected based on the clinical history, and multiple panels may be indicated if multiple phenotypes emerge. Given the frequency of associated anomalies, such investigation can greatly enhance preventative care and mitigate future risk, particularly for conditions that can result in sudden cardiac death.
Abstract 12143: Ventricular Conduction Abnormality and Outcome of Patients With Mild to Moderate Systolic Dysfunction
Authors: Mehak Dhande, Konstantinos Aronis, Floyd W Thoma, Suresh R Mulukutla, Aditya Bhonsale, Krishna Kancharla, Alaa Shalaby, Andrew Voigt, N A Mark Estes, Sandeep Jain, Samir Saba
Journal: Circulation (2022)

Introduction: In the context of mild-to-moderate systolic dysfunction (ejection fraction (EF) 36-50%), cardiac resynchronization therapy (CRT) is indicated only in patients with expected high burden of pacing but not in those with intrinsic ventricular conduction abnormalities. Hypothesis: Ventricular conduction delay is associated with a higher risk of mortality and HF hospitalization in patients with mild to moderate systolic dysfunction. Methods: We analyzed 5,966 patients with mild-to-moderate systolic dysfunction. Of those, 1,741 (29%) had a QRS duration of ≥120 milliseconds (ms). In the latter group, 68 (4%) patients were implanted with a CRT device. Patients were followed to the endpoints of death and the composite outcome of death or heart failure (HF) hospitalization. Results: Of the 1,741 patients with mild-to-moderate cardiomyopathy and wide QRS duration, 849 (51%) died and 1,004 (58%) had a HF hospitalization over a median follow-up of 3.35 years. Compared to patients with QRS&lt;120 ms, patients with QRS&gt;120 ms were at a higher risk of all-cause mortality (HR 1.11, CI 1.00-1.23, P=0.046) and of the composite of mortality or HF hospitalization (HR 1.10, CI 1.01-1.20, P=0.037) (Figure 1). Among patients with QRS&gt;120 ms, those who underwent CRT implant, had a lower risk of all-cause mortality (HR 0.44, CI 0.45-0.89, P=0.02) and of mortality or HF hospitalization (HR 0.58, CI 0.39-0.87, P=0.008). Conclusions: Among patients with HF and intermediate EF, a wide QRS is associated with higher risk of mortality and heart failure hospitalization. CRT is associated with a reduction in these adverse outcomes. Randomized trials are needed to assess role of CRT in this patient population.